The research proposed will attempt to define in some detail the biochemical processes underlying ethanol mediated liver cell destruction. Work will initially focus on the effects of alcohol on protein synthesis, using as model systems isolated rat hepatocytes in "resting culture", and hepatoma tissue culture cells capable of metabolizing alcohol. Experiments will be designed to quantitate the inhibitory effect of alcohol on cell growth and protein synthesis, to identify through the use of products and enzyme inhibitors the molecular species responsible for inhibition, and to define, using cell free protein synthesizing systems, the level at which inhibition occurs. Additional experiments will deal with the effects of alcohol on the synthesis and degradation of the major RNA species. Studies on the cell cycle and DNA synthesis are also planned. A simultaneous and complementary clinical study will also be started, using tissue obtained during the course of routine diagnostic liver biopsy in patients with alcoholic liver disease. Activity of the enzymes alcohol dehydrogenase, aldehyde dehydrogenase and 5 nucleotidase in this tissue will be determined and analyzed together with histologic, clinical and immunologic data from the standpoint of prognostic significance. The importance of genetic background in the three major groups in this study - American Indian, Chicano and Anglo - will also be assessed.